PLoS Ghostwriting Archive

Two weeks ago we blogged about a ghostwriting case involving Wyeth. So we were interested to see that PLoS Medicine has now put an entire archive of documents related to Wyeth's sophisticated ghostwriting system.

See also this editorial accompanying the archive, from PLoS Medicine's Chief Editor, Ginny Barbour: Ghostwriting: The Dirty Little Secret of Medical Publishing That Just Got Bigger. The editorial reads, in part:

If you are an editor, author, reviewer, or reader of medical journals, or if you depend on your doctor or health care provider getting unbiased information from medical journals, then the 1,500 documents now hosted on the PLoS Medicine Web site should make you very concerned and angry [1]. Because, quite simply, the story told in these documents amounts to one of the most compelling expositions ever seen of the systematic manipulation and abuse of scholarly publishing by the pharmaceutical industry and its commercial partners in their attempt to influence the health care decisions of physicians and the general public....

To Barbour's list of people-who-should-be-concerned, I'd add Ethics Board members as well as university administrators. In particular, with access to this kind of evidence about ethical standards at Wyeth, don't you think it at least possible that Ethics Boards are going to be scrutinizing research protocols extra-carefully, when those protocols are sponsored by that company? And in turn, wouldn't any researcher who knows Wyeth's now-tarnished reputation have misgivings about associating themselves with that company's name?

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Tip of the hat to Sheril Kirshenbaum, who blogs at Discover.

The persistence of the therapeutic misconception

A recent paper in BMC Medical Ethics shows that, in a small sample, a majority of research participants expressed a therapeutic misconception about the research in which they were involved. This isn't necessarily news. The notion of therapeutic misconception has been around for a long time and Applebaum et al, in 1982, finally gave a name to it. Much has been written on therapeutic misconception since that time and interestingly, it seems to have become a pitfall of human participant research that many comment on.

Here's the story: Expression of therapeutic misconception amongst Egyptians: a qualitative pilot study

There are two major ethical concerns with the TM. First, failure to appreciate correctly the risks and benefits of research participation raises concerns regarding the validity of informed consent. Indeed, understanding is an important requirement of informed consent, which itself is fundamental to ethical clinical research. Second, the presence of TM reflects the very real possibility that research participants will see themselves as patients and trust researchers as if the investigator's role was that of the physician. The resulting concern is that patients will be susceptible to exploitation, as investigators might take advantage of such misplaced trust to enroll them in clinical research. The specific concern is that patients will view an invitation to enroll in research as a professional recommendation that is intended to serve their individual treatment interests.

Therapeutic misconception (TM), according to the authors of the BMC article, comes in two forms. In the first form, participants mistakenly believe that decisions regarding randomization in a study will be individualized to their needs and will "help" them and not cause potential harm, i.e. "The study doctor will make sure that I'll get the better drug!" The second form of TM occurs when participants overestimate the degree of individual benefit that will come from enrolling in a study, i.e. "My doctor wouldn't ask me to take part if she didn't think participating would help me!" The existence of an "already-standing" relationship, especially a therapeutic or trusting one (doctor-patient, therapist-patient) can contribute to TM in a significant way.

This is arguably one of the most serious problems in human participant research, both clinical and non-clinical (and I'll say later why the concept of TM is so important in non-clinical research as well). Why is this one of the most serious problems in research ethics? First of all, it's pervasive. While this article was nicely conceptualized and well-written, it wasn't saying anything new. More participants than not think that research, to some degree, may involve personal benefit and will certainly not cause them harm. Second of all, for a moment, just imagine the opposite case. Imagine if a patient coming in for surgery to bypass his diseased coronary arteries actually thought he was undergoing an intervention related to research, instead of a routine bypass surgery for therapy. The clinical team would, no doubt, work very hard to clarify the therapeutic value of the procedure and ensure that he demonstrated understanding that this wasn't a "research study" before allowing him to consent to the surgery. As researchers, do we work as hard to ensure that human participants in research actually understand that research does not equal therapy? I don't think so. I'm not sure why.

Most of the literature on therapeutic misconception addresses the phenomenon in the context of biomedical research. I think that the therapeutic misconception is just as pervasive in many other types of human participant research, from what I've seen and read. Students involved in educational research believe that their trusted professors wouldn't expose them to a useless learning or teaching intervention as part of an educational study. They may, in turn, also believe that participation in a study by their professor will augment their knowledge or help them be in a position of advantage in terms of learning. Participants involved in qualitative interviews may believe that it is a form of beneficial talk-therapy. Those who volunteer for psychology studies may well harbour false hope that the studies will offer them individualized help. While it's true that, in some cases, students involved in educational research may learn new skills that will help them in their academic life and those involved in qualitative interviews may feel empowered from telling their stories, research participants must be made to understand that research study involvement cannot guarantee personal or individualized benefit. How to ensure this? First, it must be more than simply a routine statement on a consent form. As I've said before, consent is much more than a form. It's a process that is merely represented, in many cases, by a form. Concepts like randomization, risk and benefit must be clearly explained during the research process and ideally, participants should be provided with understandable information about the goals and purposes of the study. Care must be taken in recruitment processes to avoid role confusion — the caring physician may not be the ideal person to recruit her own patients for a study and the engaged and passionate professor might be better to have a research assistant introduce a study to a classroom of students.

Each study and potential case of TM is different. Researchers must be aware of the kinds of messages that they explicitly (through consent forms) and implicitly (through "already-standing" therapeutic relationships) send to participants when discussing benefit and obtaining consent. Research ethics boards need to be vigilant about reading consent forms carefully, examining consent processes, identifying "already-standing" therapeutic relationships and engaging in discussions with researchers about these kinds of issues so that pitfalls, like TM, can be avoided.

Research Ethics in Space

Yes, in space. We've blogged before about ethical issues related to research done overseas. But research ethics in space? That's a new one for us.

Check out this conversation with Paul Root Wolpe, from the New York Times: Scientist Tackles Ethical Questions of Space Travel

Q. AS NASA’S CHIEF BIOETHICIST, WHAT DOES YOUR WORK INVOLVE?

A. I’m an adviser to the chief medical officer for the agency. I don’t make decisions. Instead, I analyze situations and policies and offer bioethical perspectives on specific problems.

NASA does hundreds of research studies. Every astronaut who goes into space is, essentially, a human research subject. NASA’s looking at the effects of weightlessness, of G-forces and radiation on the human body. One of the things I do is look over the research protocols and make sure they are in compliance with earth-bound regulations about informed consent and health and safety. I also try to help solve some of the thorny ethical problems of medical care for astronauts in space....

A few quick thoughts:

1) My first thought is about the challenges such a unique research setting poses for Wolpe, who, from the sounds of it, essentially acts as a one-man ethics board for NASA. Nancy blogged back in June about the fact that research ethics boards typically learn, and improve, by a process of trial and error. The number of trips into space, and hence the number of space-based experiments, is tiny. That makes it hard for anyone to build up a base of expertise — assuming, as seems reasonable, that there are at least a few ethical peculiarities unique to doing research in space.

2) Nor is there going to be a body of literature to draw upon. There's no Journal of Space-Based Research Ethics. So there won't be any place to look to see how other people in the field have dealt with the same issues.

3) But of course, research in space isn't totally unique: it has parallels, though maybe not precise ones. NASA isn't technically military, but it seems reasonable to expect that research during a space mission would share some things in common with research on military personnel. And given that astronauts are basically trapped in a shuttle or space station, research on them would have something in common with research on institutionalized individuals, like prisoners.

4) Unlike most research, research on board a shuttle or space station probably blurs the line between researcher and subject. In many cases, everyone on board will play both roles. That's unavoidable, but it's also likely to require additional safe-guards.

5) Finally, to the extent that the military analogy is valid, the US Army is a pretty good organization to look to in terms of having well-worked-out policies to protect their personnel in research contexts. (For example, Army Regulation 70-25 [PDF here.] rightly forbids use of military-legal penalties against personnel who decline to participate in research.) I don't know much about how well the Army has done at applying those policies, but having such policies in place is a very good start. And if their policies are sound ones, then Wolpe isn't working entirely in a vacuum; he's not merely left to boldly go where no research ethicist has gone before.

Ghost-Writing and the Corruption of Research

Earlier today I posted, over at the Business Ethics Blog, an item called Wyeth, 'Ghost-Writing' and Conflict of Interest. It was based on this article by Natasha Singer, writing for the NY Times: Medical Papers by Ghostwriters Pushed Therapy

Newly unveiled court documents show that ghostwriters paid by a pharmaceutical company played a major role in producing 26 scientific papers backing the use of hormone replacement therapy in women, suggesting that the level of hidden industry influence on medical literature is broader than previously known.

The articles, published in medical journals between 1998 and 2005, emphasized the benefits and de-emphasized the risks of taking hormones to protect against maladies like aging skin, heart disease and dementia. That supposed medical consensus benefited Wyeth, the pharmaceutical company that paid a medical communications firm to draft the papers, as sales of its hormone drugs, called Premarin and Prempro, soared to nearly $2 billion in 2001....

On the Business Ethics Blog, I focused on the fact that the company involved, Wyeth, completely missed the point in arguing that the articles it paid to have ghost-written were scientifically sound. Wyeth's argument misses the point, I said, because the problem with conflict of interest is not that it typically results in bad outcomes; the problem, rather, is that it shakes our confidence in the reliability of a decision-maker and possibly in an entire institution.

What I didn't touch on in that blog entry is the role of the physician-researchers whose names appeared on the ghost-written papers. Clearly, their cooperation in the charade is crucial. And some of them — maybe all of them — also fail to see the true problem with ghost-writing. Check out this quotation, from Dr. Gloria Bachmann, one of the medical professionals involved:

“There was a need for a review article and I said ‘Yes, I will review the draft and make sure it is accurate,’ ” Dr. Bachmann said in an interview Tuesday. “This is my work, this is what I believe, this is reflective of my view.”

Once again, this misses the point entirely. The problem is not whether the paper that resulted from the ghost-writing process was sound, or whether it represented a point of view that Dr. Bachmann could stand behind. The point is: how can we be sure? How do we know just how much, or how little, influence Wyeth, had on the paper that resulted? It's not that we don't trust Dr. Bachmann. I, for one, am willing to give her the benefit of the doubt. The problem is that the process used to generate the paper that bore her name was one highly likely to cast doubt upon the process of scientific publication. I wonder, if more researchers saw things that way, would they be more hesitant to participate in that process?